New solvent models, sampling methods and maintenance of Amber software

描述（由申请人提供）：本提案响应PAR-11-028，软件的持续开发和维护：本计划的目标是支持现有软件的持续开发、维护、测试和评估。Amber是一个流行的软件包，授权给800多家学术和工业机构，用于模拟分子系统的结构，热力学和动力学性质。流行的Amber ff99SB力场有885个引用，它是由PI Carlos Simmerling在Stony Brook开发的。Simmerling小组是负责Amber维护和开发的六个学术小组之一。使用Amber和其他软件包的计算分子动力学模拟已经成为理解生物分子机制的实验研究和发现抑制它们的药物的必要对应物。流行的虚拟筛选程序DOCK直接与Amber接口。这里提出的软件改进的一个目标是减少开发新药所需的时间。我们在这里提出了Amber的新发展，解决了该领域最紧迫的需求。目标1，溶剂化：我们将采用改进的溶剂化模型：(a) SEA半显式水模型和(b)新的广义Born模型。目标2，采样：我们将增加快速和有针对性的采样方法：(a)通用工具哈密顿交换和热复制交换分子动力学的变体，(b)新的有限数据建模方法，该方法对受稀疏和噪声数据影响的构象进行采样；(c)用于采样环路构象的非常快速的Kinetic-Loop-Closure和Constrained-Loop-Closure方法，以及(d)用于计算生物分子两种不同构象之间自由能差的限制和过渡方法。我们将把我们最近开发的算法纳入Amber的生产代码中进行分发，并使用CUDA将代码移植到最近开发的GPU版本的Amber。

DESCRIPTION (provided by applicant): This proposal responds to PAR-11-028, Continued Development and Maintenance of Software: The goal of this program is to support the continued development, maintenance, testing and evaluation of existing software. Amber is a popular software package, licensed to over 800 academic and industry institutions, for simulating the structural, thermodynamic and kinetic properties of molecular systems. There are 885 citations to the popular Amber ff99SB force field, developed at Stony Brook by PI Carlos Simmerling. The Simmerling group is one of the six academic groups responsible for Amber maintenance and development. Computational Molecular Dynamics simulations using Amber and other software packages have become essential counterparts to experimental research for understanding the mechanisms of biomolecules, and for discovering drugs to inhibit them. The popular virtual screening program called DOCK interfaces directly with Amber. One goal of the software improvements proposed here is to reduce the time it takes to develop new drugs. We propose here new developments for Amber, addressing the most pressing needs of the field. Aim 1, Solvation: We will incorporate improved solvation models: (a) the SEA semi-explicit water model and (b) a new Generalized Born model. Aim 2, Sampling: We will add fast and targeted sampling methods: (a) variants of the general tools Hamiltonian exchange and thermal Replica Exchange Molecular Dynamics, (b) the new Modeling with Limited Data method, which samples conformations subject to sparse and noisy data; (c) the very fast Kinetic-Loop-Closure and Constrained-Loop-Closure methods for sampling loop conformations, and (d) the Confine and Transition method, which computes free- energy differences between two different conformations of a biomolecule. We will incorporate our recently developed algorithms into the Amber production code for distribution, and port the codes to the recently developed GPU version of Amber using CUDA.